The response of receptors to hormones is particularly important in the development of a number of diseases, including cancer. Hormone resistant cancers include certain breast, endometrial, ovarian and prostate cancers.
Breast cancer is the leading cause of death among American women between the ages of 20 and 59. Among a variety of established etiological factors linked to breast cancer, the steroid hormone estrogen (17-β-estradiol; E2) has long been implicated in disease pathogenesis. Numerous animal studies have revealed that E2 can induce and promote breast cancer, while estrogen ablation therapy or the administration of antiestrogens can oppose these effects. The physiological effects of E2 in the breast are mediated by cognate receptors that are expressed as two structurally related subtypes, estrogen receptor α (ERα) and β (ERβ). ERα is the predominant receptor isoform expressed in breast cancer cells, and approximately 70% of breast cancer patients score positive for ERα at diagnosis. ERα is therefore a predictive factor with respect to breast cancer development and hormone sensitivity status. Endocrine therapy, which seeks to block ER-mediated mitogenic signaling, has emerged as one of the most important systemic therapies in breast cancer management. However, therapeutic resistance, either inherent (de novo resistance) or acquired during treatment (acquired resistance) remains a significant clinical roadblock to effective disease management.
Prostate cancer is the second leading cause of cancer death among males in the United States. Although survival rates are good for prostate cancer that is diagnosed early, the treatments for advanced disease are limited to hormone ablation techniques and palliative care. Hormone ablation techniques (orchiectomy and anti-androgen treatments) generally allow only temporary remission of the disease. It usually recurs within 1-3 years of treatment, with the recurrent tumors no longer requiring androgens for growth and survival. Therapy with conventional chemotherapeutic agents, such as progesterone, estramustine and vinblastine, has also not been demonstrated to be effective to halt progression of the disease.